synthesis and catalytic functionalization of biologically active indoles

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List of Abbreviations VI M Molar Me Methyl MeOH Methanol min Minute MOM Methoxymethyl ether Nf Nonaflate NMR Nuclear Magnetic Resonance OAc Acetate OMe Methoxy o Ortho p Para Ph Phenyl PhH Benzene PhMe Toluene pin Pinacol Piv Pivaloyl iPr iso-Propyl R Organic rest rt Room temperature SEM (Trimethylsily)ethoxymethyl Sphos Dicyclohexylphosphino-2',6'-dimethoxybiphenyl TBAB Tetrabutylammonium bromide TBAI Tetrabutylammonium iodide TBDMS tert-Butyldimethylsilyl TBDPS tert-Butyldiphenylsilyl TBS tert-Butyldimethylsilyl Tf Triflate THF Tetrahydrofuran TIPS Triisopropylsilyl TON Turnover number Tos Tosyl TPABr Tetrapropylammonium bromide X Halide Xantphos 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene Xphos 2-Dicyclohexylphosphino-2�,4�,6�-triisopropylbiphenyl Y Halide
Preface The search for drugs is an old human dream and constitutes still a real challenge for scientists. Already alchemists sought for the one drug, the Elixir healing all human ailments. Today, the growing knowledge in pharmacy and biology makes the search for novel drugs complex and difficult. Therefore it is not surprising that organic chemists are interested in the development of easy accessible synthesis to new potential drugs. An interesting target for drug design is the serotonin (5-hydroxytryptamine 5-HT) receptor ligand. It is one of the oldest known neurotransmitter in the central nervous system and responsible for controlling our body temperature, mood, sexual drive and sleep rhythm. This hormone is implicated in many diseases like schizophrenia, anxiety, obesity and Alzheimer’s disease. Based on the indole skeleton it is an interesting building block which is of importance to the pharmaceutical industry. The application of new 5-HT receptor ligands against these diseases demanded an easy access to indole derivatives and wide scope of functionalization. Metal-catalyzed cross-coupling reactions have profoundly changed the protocols for the construction of natural products, building blocks of supermolecular chemistry and lead compounds in medicinal chemistry from simpler entities. The development of efficient new carbon-carbon bond forming reactions by metalcatalyzed cross-coupling has continued to progress dramatically and some of the reactions are finding industrial application on the multipleton scale. Furthermore new protocols for C-N and C-O couplings have been introduced and find particular use in the synthesis of biologically active compounds for pharmaceutical application. Cross-coupling reactions play an important role in the development of new 5-HTreceptor ligands as well. Finding the optimized conditions in C-N- or C-O- bond forming processes is one of the key steps in the synthesis of new indole derivatives. VII
Page 1 and 2: Leibniz-Institut für Katalyse e. V
Page 3 and 4: Für meine Eltern Siegfried und Ker
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Page 9: List of Abbreviations Ac Acetyl aq
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1 Palladium-catalyzed Coupling Reac
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3 Publications 3.1 Titanium-Catalyz
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1092 N. Schwarz et al. LETTER Table
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1094 N. Schwarz et al. LETTER 2,6-d
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3 Publications 84 3.2 Zinc-Promoted
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Table 2: Reaction of N-methyl-N-phe
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Am. Chem. Soc. 2002, 124, 15168 - 1
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A novel palladium catalyst for the
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Table 2. Reaction of different amin
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3 Publications 94 Experimental Data
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3 Publications 96 (q); 115.3 (d, J
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3 Publications 98 3.4 Palladium-Cat
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PAPER Coupling Reactions of Electro
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3 Publications 108 3.5 Synthesis of
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Scheme 2 Ti-catalyzed synthesis of
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mixture was used for the synthesis
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7.11 (ddd, 1H, J = 8.0 Hz, J = 7.0
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FULL PAPER DOI: 10.1002/ejoc.200800
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Synthesis of Potential 5-HT 6 Recep
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FULL PAPER DOI: 10.1002/ejoc.200700
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Synthesis of Indole-2,3-dicarboxyla
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3 Publications 132 3.8 Selective Re
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8 7 N R N R OH CO2Et CO2Et OH indol
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mixture was stirred at 78 C for 3 m
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3.89 (s, 2H, H-10), 4.27 (s, 2H, H-
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DOI: 10.1002/cssc.200700160 General
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Zn-Catalyzed Hydroamination of Term
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Zn-Catalyzed Hydroamination of Term
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3 Publications 146 3.10 Zn-Catalyze
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Over the past years, we investigate
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3 Publications 150 3.11 First Synth
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4608 K. Alex et al. / Tetrahedron L
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Publikationen 1 Titanium-Catalyzed
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synthesis and catalytic functionalization of biologically active indoles

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